Lifestyle-related disease arising from deteriorations of living habit such as supernutrition and underexercise is a major social concern today. Lifestyle-related disease involves various states of disease such as obesity, diabetes mellitus, hyperlipemia and hypertension, and these states of disease are gathering considerable attention as multiple risk factor syndrome that may be an underlying disease of arteriosclerosis. Moreover, this is a matter of concern not only in humans but also in pet animals such as dogs and cats.
Obesity is roughly classified into subcutaneous fat-type obesity resulting from accumulation of subcutaneous fat and visceral fat-type obesity resulting from accumulation of intra-abdominal fat.
Visceral fat-type obesity is a disease which is accompanied by hyperlipemia, glucose tolerance abnormality, and hypertension at high rates and also characterized by strong insulin resistance so that it is known as multiple risk factor syndrome. Moreover, visceral fat accumulation is not only found in obese individuals but also observed in persons within the normal body weight range and is likely to accompany the multiple risk referred to above (BIO Clinica, September, 2000 expanded issue, 16-55). This, visceral fat accumulation triggers insulin resistance, diabetes mellitus, hyperlipemia, hypertension and the like. Matsuzawa et al. coined the term “visceral fat syndrome” for this disease entity (Diabetes/Metabolism Reviews, 13, 3-13, 1997). “Syndrome X” as proposed by G. M. Reaven (Diabetes, 37, 1595-1607, 1988), “deadly quartet” as proposed by N. M. Kaplan (Archives of Internal Medicine, 149, 1514-1520, 1989), and “insulin-resistance syndrome” as proposed by R. A. DeFronzo (Diabetes Care, 14, 173-194, 1991) signify the same disease entity.
The therapy of obesity generally consists of diet therapy and exercise therapy, and drug therapy is indicated in serious obesity cases. However, these therapeutic regimens are recommended or prescribed to patients by medical institutions, and are not directed to the so-called candidate patients in the reserve. Moreover, appetite suppressants, inhibitors of digestion and absorption of carbohydrate and fat as energy sources, and energy consumption promoters can be mentioned as antiobesity agents. However, appetite suppressants and inhibitors of digestion and absorption do not positively lower visceral fat, and energy consumption promoters do not specifically lower visceral fat.
Japanese Kokai Publication Hei-11-187843 discloses that administration of an extract of Cassia nomame having fat absorption inhibitory action and an extract of Morus bombycis having carbohydrate absorption inhibitory action in combination leads to inhibition of body weight gain and reductions in subcutaneous fat and visceral fat. Regarding other substances of the natural origin, it is known that substances derived from highly unsaturated oils such as fish oil and vegetable oil, e.g. linseed oil and perilla oil (Japanese Kokai Publication Hei-10-231495), or conjugated isomerized highly unsaturated fatty acids (Japanese Kokai Publication 2000-144170) have an accumulated visceral fat lowering function, that an amylase inhibitor derived from wheat (Japanese Kokai Publication Hei-09-194390) inhibits visceral fat accumulation, and that D-xylose and/or L-arabinose (Japanese Kokai Publication Hei-07-309765 and Japanese Kokai Publication Hei-07-242551) inhibits accumulation of body fat (subcutaneous fat and visceral fat).
Diabetes mellitus is a disease the chief manifestation of which is chronic hyperglycemia resulting from a deficiency in insulin activity, and not less than 90% of diabetics are those with type II diabetes (non-insulin dependent diabetes mellitus; NIDDM). The number of diabetic patients in Japan has increased dramatically from 1.57 million in 1993 to 2.18 million in 1996 (a patient survey of the Health and Welfare Ministry). Furthermore, according to the Health and Welfare Ministry's diabetes census undertaken in November 1997, the persons strongly suspected to be diabetic (inclusive of those on therapy) numbered 6.9 million and the sum of this number and the number of individuals in whom diabetes could not be ruled out was estimated at 13.7 million. Thus, besides the sharply increasing number of diabetics, the number of individuals in the reserve and not on therapy by medical institutions is by far large, and this is a matter of serious concern.
The therapy of diabetes mellitus includes diet therapy and exercise therapy, and in cases not sufficiently responsive to these therapies, drug therapy is superimposed. The drug therapy includes insulin therapy and administration of oral hypoglycemic drugs. As oral hypoglycemic drugs, there can be mentioned sulfonylurea derivatives such as tolbutamide and glibenclamide; biguanides such as buformin and metformin; α-glucosidase inhibitors such as acarbose and voglibose; and insulin resistance improving drugs such as troglitazone and pioglitazone.
In diet therapy, the patient is recommended to refrain from overeating and adhere to a legitimate calorie intake and, if one is obese, instructed to make efforts to slim down to the standard body weight. As foodstuffs to be used in diet therapy, assorted foods for preparation of diets for diabetics, which are special-use foods approved by the Health and Welfare Ministry, are known. However, these are no more than the so-called low-calorie, balanced-nutrition foods, and cannot be considered to have intrinsic therapeutic efficacy for diabetes.
Furthermore, these therapies are prescribed for diabetics by medical institutions and not directed to the so-called diabetics in the reserve who outnumber the diabetics by a large margin. There is accordingly a demand for a composition effective for preventing or ameliorating diabetes mellitus in the form of a food/beverage, such as food with health claims (food for specified health uses and food with nutrient function claims) or health food, or a drug (inclusive of a quasi-drug) to which access may be easily had by any one not associated with medical institutions.
The incidence of diabetes has been on the steady increase in domestic or pet animals, too, and development of a composition effective for preventing or ameliorating diabetes in domestic and pet animals is being desired.
Japanese Kokai Publication Hei-01-233217 discloses an antidiabetic composition comprising curcumenone, the extract of Curcuma aromatica, the family Zingiberaceae, as an active ingredient. Japanese Patent Hei-06-192086 discloses an antidiabetic composition comprising
(4S,5S)-(+)-germacrone-4,5-epoxide, the extract of Curcuma aromatica, as an active ingredient. Curcuma aromatica is known to be a crude drug but has not been cleared for use as a food additive.
Licorice and its aqueous extract are in use as crude drugs having analgesic/anticonvulsant and expectorant actions or as foods. Since the chief component glycyrrhizin (glycyrrhizinic acid) is about 200 times as sweet as sucrose, the “licorice extract” obtainable by extracting licorice with water or an alkaline aqueous medium is a food additive for use as a sweetener as well (Annotated List of Additives in Available Books, page 163, Japanese Food Additives Association, 1999). Its physiologic actions so far known are adrenocortical electrolyte or glycocorticoid-like action, estrogen-like action, testosteron production-inhibitory action, antitussive action, antiinflammatory action, antiallergic action, detoxicating action, hyperlipemia-improving action, gastric mucosal cell cyclic-AMP concentration increasing action, experimental liver impairment preventing or ameliorating action, antiviral action, interferon-inducing action, anticaries action, tumor promoter inhibitory action, cytosolic Ca2+ lowering action, phospholipase A2 inhibitory action, LTB4 and PGE2 production inhibitory action, and platelet activating factor production inhibitory action, among others. Furthermore, licorice is one of the components of the traditional Chinese medicine Byakko-ka-Ninjin-To which is prescribed for the diabetes-associated intense dry-mouth, polyposia, and polyuria and, like gypsum, anemarrhena, and ginseng which are also formulated, an aqueous extract of licorice reportedly has a hypoglycemic action (I. Kimura, et al.: Phytotheraphy Research, 13, 484-488, 1999).
The licorice residues which remain after extraction of glycyrrhizin from licorice with water or an aqueous alkaline medium are known to have a hepato-tonic (hepatoprotectant) action and/or an antiinfective action (Japanese Kokai Publication Hei-09-143085), an immunopotentiating action (Japanese Kokai Publication Hei-05-262658), and an antiviral action (Japanese Kokai Publication Hei-01-175942). Furthermore, the “licorice oily extract” which can be obtained by extracting the residues of licorice after aqueous washing with ethanol, acetone, or hexane is an antioxidant for use as a food additive (Annotated Lists of Additives in Available Books, page 164, Japanese Food Additives Association, 1999). The licorice oily extract is known to have antibacterial activity against Helicobacter pylori (Japanese Kokai Publication Hei-10-130161, Japanese Kokai Publication Hei-08-119872). However, it is not known that said licorice residues after extraction of glycyrrhizin or said licorice oily extract ever has a visceral fat lowering action, a hypoglycemic action, a lipid metabolism improving action, or a blood pressure elevation inhibitory action.
Incidentally, it is long known that an excessive intake or prolonged use of licorice induces pseudoaldosteronism inclusive of hypertension, edema, and hypokalemia. This condition is caused by glycyrrhizin which is the main component of licorice. It is also reported that hypertension may be elicited by glycyrrhetinic acid which is a hydrolyzate of glycyrrhizin (H. Siguruonsdottir, et al.: Journal of Human Hypertension, 15, 549-552, 2001). Thus, a licorice aqueous extract which contains the hydrophilic fraction of licorice and is composed predominantly of glycyrrhizin induces hypertension.
As tropical plants relegated to the genus Curcuma, the family Zingiberaceae, of Tropical Asian origin, several varieties such as Curcuma longa, Curcuma aromatica, Curcuma zedoaria, and Curcuma xanthorrhiza are known. Among these, Curcuma longa is commonly called “turmeric” and known to be one of the component spices of curry. This is not only used as a foodstuff but, because the principal component curcumin of Curcuma longa is a yellow dye (natural color), this plant or an extract thereof (curcuma dye) is used as a dyestuff or a coloring agent (a food additive). As a herbal medicine in traditional therapies such as Kampo (traditional Chinese medicine) of China, Ayur-Veda of India, and Jamu of Indonesia, it is long known that Curcuma longa has hemostatic, stomachic, antibacterial, and antiinflammatory actions, and actually this plant is still in use as a medicine. Furthermore, the efficacy of turmeric (Curcuma longa) and its principal component curcumin is attracting attention and has been found to have various physiologic actions such as an antioxidant action, a cholagogue action (a choleretic action), a visceral (liver, pancreas) function-potentiating action, an anti-tumor effect, a lipid metabolism improving action, and a skin lightening action.
However, it is not known that turmeric or its extract ever has a visceral fat lowering action, a hypoglycemic action, or a blood pressure elevation inhibitory action.
Clove is the flower-bud, leaf, or flower of Syzygium aromaticum or Eugenia caryophyllata of the family Myrtaceae and is known to be one of spices. By virtue of its antibacterial/bactericidal action and an analgesic/anesthetic action, clove has been used for many generations not only as a breath sweetener or an antiodontalgic but also as a stomachic in the realm of crude drugs and herbal medicines (Kampo medicine). Furthermore, a clove extract has been applied as an antioxidant for food additive use. However, it is not known that clove or its extract ever has visceral fat lowering action, a hypoglycemic action, a lipid metabolism improving action or a blood pressure elevation inhibitory action.
Cinnamon or cassia is the bark of Cinnamomum cassia, C. zeylanicum, or C. loureirii of the family Lauraceae. Cinnamon has antibacterial and antioxidant actions and has long been used as one of spices and its bark has been used in medicinal applications. However, it is not known that cinnamon or its extract has a visceral fat lowering action, a hypoglycemic action, a lipid metabolism improving action, or a blood pressure elevation inhibitory action.